Department of Pathology, Tohoku University Graduate School of Medicine, Sendai, 980-8575, Japan.
Hum Pathol. 2013 Aug;44(8):1586-96. doi: 10.1016/j.humpath.2013.01.004. Epub 2013 Mar 19.
Non-small cell lung carcinoma is one of the most common leading causes of cancer mortality, and studying the features of intratumoral vessels, especially their generation and maturation, has become more important because of the recent application of antiangiogenic therapy. Vasohibin-1 has been recently considered one of the immunohistochemical markers for identifying neovascularization in archival materials. In addition, the functional maturation of blood vessels is considered to be related to pericyte formation around endothelial cells. Therefore, in this study, we evaluated the status of angiogenesis and maturation of intratumoral blood vessels in 93 patients with non-small cell lung carcinoma (50 with adenocarcinoma and 43 with squamous cell carcinoma) using immunohistochemistry of vasohibin-1, endoglin, CD31, and nestin. The vasohibin-1/CD31-positive ratio was significantly (P = .03) correlated with the Ki-67/CD31 ratio, confirming that the vasohibin-1/CD31-positive ratio represented the status of neovascularization in lung cancer. There were no statistically significant differences in vasohibin-1/CD31 ratios between adenocarcinoma and squamous cell carcinoma in both inner (P = .39) and outer areas (P = .36) of the tumor. The vasohibin-1/nestin-positive ratio, which represents the degrees of vascular maturation in proliferative vessels, was significantly lower in inner areas of adenocarcinoma (0.4 ± 0.1) than those in squamous cell carcinoma (0.8 ± 0.1) (P = .02). These results demonstrated that the degrees of maturation in newly formed blood vessels were less developed in inner areas of squamous cell carcinoma than adenocarcinoma, which may account partly for the complications of antivascular endothelial growth factor therapy more frequently detected in patients with squamous cell carcinoma.
非小细胞肺癌是癌症死亡的最常见主要原因之一，由于最近应用了抗血管生成治疗，研究肿瘤内血管的特征，尤其是其生成和成熟，变得更加重要。血管抑素-1 最近被认为是识别存档材料中新血管形成的免疫组织化学标志物之一。此外，血管的功能成熟被认为与内皮细胞周围周细胞的形成有关。因此，在这项研究中，我们使用血管抑素-1、内胚层蛋白、CD31 和巢蛋白的免疫组织化学方法，评估了 93 例非小细胞肺癌患者（50 例腺癌和 43 例鳞状细胞癌）肿瘤内血管的血管生成和成熟状态。血管抑素-1/CD31 阳性比值与 Ki-67/CD31 比值显著相关（P =.03），证实血管抑素-1/CD31 阳性比值代表肺癌新生血管的状态。在肿瘤的内外区，腺癌和鳞状细胞癌的血管抑素-1/CD31 比值均无统计学差异（P =.39 和 P =.36）。血管抑素-1/巢蛋白阳性比值代表增殖性血管的血管成熟程度，腺癌的内区明显低于鳞状细胞癌（0.4 ± 0.1 比 0.8 ± 0.1）（P =.02）。这些结果表明，鳞状细胞癌的内区比腺癌的新形成血管的成熟程度较低，这可能部分解释了在鳞状细胞癌患者中更频繁地检测到抗血管内皮生长因子治疗的并发症。
